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LeukemiaPhase 2NCT00003910

Methotrexate With or Without Cyclophosphamide in Treating Patients With Lymphocytic Leukemia

A Phase 2 study testing Cyclophosphamide, Methotrexate and Prednisone in people with Leukemia, run by Eastern Cooperative Oncology Group at 68 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of methotrexate with or without cyclophosphamide in treating patients who have lymphocytic leukemia with neutropenia or anemia. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia
What is being tested?
Cyclophosphamide, Methotrexate and Prednisone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
59 participants
Where
68 sitesUnited States
Study dates
15 Sep 1999to Mar 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Phenotypic studies from peripheral blood showing CD3+, CD57+ cells greater than 400/mm3 or CD8+ cells greater than 650/mm3 within eight weeks prior to registration
  • Evidence for clonal T-cell receptor gene rearrangement within one year prior to registration
  • At least one of the following: Severe neutropenia less than 500/mm3, neutropenia associated with recurrent infections, symptomatic anemia, or transfusion-dependent anemia
  • Bilirubin ≤ 2.0 mg/dl, SGOT(AST) ≤ 1.5 times normal, and Creatinine ≤ 2.0 mg/dl within 4 weeks prior to registration
  • ECOG performance status of 0-2
  • At least 18 years of age
  • Written informed consent

Who cannot join

  • Prior therapy with oral MTX or oral Cy
  • Previous or concurrent malignancies except inactive non-melanoma skin cancer, in situ carcinoma of the cervix, or other cancer if the patient has been disease free for over 5 years
  • Pregnant or breast-feeding for female patients
  • Serious medical illness, other than that treated by the study, which would limit survival to less than 2 years, or psychiatric condition which would prevent informed consent
  • Note: to be eligible for step 2 of this study, patients were required to have no response after at least 4 months of methotrexate treatment.

Trial locations and contacts

68 sites in 1 country.

68 sites in 1 country

United States68 sites

  • McFarland Clinic, PC

    Ames, Iowa, 50010

  • Aurora Presbyterian Hospital

    Aurora, Colorado, 80012

  • Rush-Copley Cancer Care Center

    Aurora, Illinois, 60504

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21231-2410

  • Boulder Community Hospital

    Boulder, Colorado, 80301-9019

  • Fairview Ridges Hospital

    Burnsville, Minnesota, 55337

  • Aultman Cancer Center at Aultman Hospital

    Canton, Ohio, 44710-1799

  • Robert H. Lurie Comprehensive Cancer Center at Northwestern University

    Chicago, Illinois, 60611-3013

  • Penrose Cancer Center at Penrose Hospital

    Colorado Springs, Colorado, 80933

  • Mercy and Unity Cancer Center at Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • St. Anthony Central Hospital

    Denver, Colorado, 80204

  • Porter Adventist Hospital

    Denver, Colorado, 80210

  • Presbyterian - St. Luke's Medical Center

    Denver, Colorado, 80218

  • St. Joseph Hospital

    Denver, Colorado, 80218

  • Rose Medical Center

    Denver, Colorado, 80220

  • CCOP - Colorado Cancer Research Program

    Denver, Colorado, 80224-2522

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • Swedish Medical Center

    Englewood, Colorado, 80110

  • Evanston Northwestern Healthcare - Evanston Hospital

    Evanston, Illinois, 60201-1781

  • Mercy and Unity Cancer Center at Unity Hospital

    Fridley, Minnesota, 55432

  • St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center

    Grand Junction, Colorado, 81502

  • North Colorado Medical Center

    Greeley, Colorado, 80631

  • Penn State Cancer Institute at Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • Hutchinson Area Health Care

    Hutchinson, Minnesota, 55350

  • Methodist Cancer Center at Methodist Hospital

    Indianapolis, Indiana, 46202

  • Joliet Oncology-Hematology Associates, Limited - West

    Joliet, Illinois, 60435

  • Borgess Medical Center

    Kalamazoo, Michigan, 49001

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007-3731

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • Gundersen Lutheran Center for Cancer and Blood

    La Crosse, Wisconsin, 54601

  • Central Pennsylvania Hematology and Medical Oncology Associates, PC

    Lemoyne, Pennsylvania, 17043

  • Lewistown Hospital

    Lewistown, Pennsylvania, 17044

  • North Shore Oncology and Hematology Associates, Limited - Libertyville

    Libertyville, Illinois, 60048

  • St. Rita's Medical Center

    Lima, Ohio, 45801

  • Meeker County Memorial Hospital

    Litchfield, Minnesota, 55355

  • Sky Ridge Medical Center

    Lone Tree, Colorado, 80124

  • Hope Cancer Care Center at Longmont United Hospital

    Longmont, Colorado, 80501

  • McKee Medical Center

    Loveland, Colorado, 80539

  • Medical Center of Central Georgia

    Macon, Georgia, 31208

  • HealthEast Cancer Care at St. John's Hospital

    Maplewood, Minnesota, 55109

  • Minnesota Oncology Hematology, PA - Maplewood

    Maplewood, Minnesota, 55109

  • Mercy Cancer Center at Mercy Medical Center - North Iowa

    Mason City, Iowa, 50401

  • Saint Anthony Memorial Health Centers

    Michigan City, Indiana, 46360

  • Froedtert Hospital and Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Medical College of Wisconsin Cancer Center

    Milwaukee, Wisconsin, 53226

  • Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • Hennepin County Medical Center - Minneapolis

    Minneapolis, Minnesota, 55415

  • Fox Chase Cancer Center - Philadelphia

    Philadelphia, Pennsylvania, 19111-2497

  • St. Mary - Corwin Regional Medical Center

    Pueblo, Colorado, 81004

  • McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center

    Reading, Pennsylvania, 19612-6052

  • Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center

    Robbinsdale, Minnesota, 55422-2900

  • CCOP - Metro-Minnesota

    Saint Louis Park, Minnesota, 55416

  • Park Nicollet Cancer Center

    Saint Louis Park, Minnesota, 55416

  • Regions Hospital Cancer Care Center

    Saint Paul, Minnesota, 55101

  • HealthEast Cancer Care at St. Joseph's Hospital

    Saint Paul, Minnesota, 55102

  • United Hospital

    Saint Paul, Minnesota, 55102

  • St. Francis Cancer Center at St. Francis Medical Center

    Shakopee, Minnesota, 55379

  • Siouxland Hematology-Oncology Associates, LLP

    Sioux City, Iowa, 51101

  • Mercy Medical Center - Sioux City

    Sioux City, Iowa, 51104

  • St. Luke's Regional Medical Center

    Sioux City, Iowa, 51104

  • Mount Nittany Medical Center

    State College, Pennsylvania, 16803

  • North Suburban Medical Center

    Thornton, Colorado, 80229

  • Carle Cancer Center at Carle Foundation Hospital

    Urbana, Illinois, 61801

  • CCOP - Carle Cancer Center

    Urbana, Illinois, 61801

  • Ridgeview Medical Center

    Waconia, Minnesota, 55387

  • Exempla Lutheran Medical Center

    Wheat Ridge, Colorado, 80033

  • HealthEast Cancer Care at Woodwinds Health Campus

    Woodbury, Minnesota, 55125

  • Minnesota Oncology Hematology, PA - Woodbury

    Woodbury, Minnesota, 55125

Other trials in United States

About this study

Official title: A Phase II Study of Initial Treatment With Methotrexate in Large Granular Lymphocytic (LGL) Leukemia

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of methotrexate with or without cyclophosphamide in treating patients who have lymphocytic leukemia with neutropenia or anemia.

Read the detailed description

LGL leukemia is characterized by clonal expansion of cytotoxic T cells. Prominent clinical features include neutropenia, anemia, and rheumatoid arthritis. The terminal effector memory phenotype (CD3+/CD8+/CD57+/CD45RA+/CD62L-) of leukemic LGL suggest a pivotal chronic antigen driven immune response. LGL survival is then promoted by PDGF and IL-15, resulting in global dysregulation of apoptosis and resistance to normal pathways of activation-induced death. These pathogenic features explain why treatment of LGL leukemia is based on immunosuppression therapy. However, no standard therapy has been established due to the absence of large prospective trials.

Oral low dose MTX has been shown to be efficacious in the treatment of neutropenia. However, response to MTX is slow, requiring several months for the neutrophil count to increase above 500/mm3. Also, complete clinical remission may not be achieved until after one year of MTX therapy. Oral Cy has been the primary drug used for the treatment of severe transfusion-dependent anemia. Beneficial clinical effects are seen despite this treatment having no apparent effect on the abnormal LGL clone. Normal hematocrits are maintained after cessation of Cy and these results contrast the effects seen with MTX, in which clinical remissions are often associated with the disappearance of the clone.

This phase II trial undertaken by the Eastern Cooperative Group (ECOG) was initiated to investigate the mechanism of treatment response in patients with LGL leukemia, who need treatment for anemia or neutropenia.

Conditions
Leukemia
Keywords
stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, T-cell large granular lymphocyte leukemia, LGL clone
Medical subject headings
Leukemia, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Large Granular Lymphocytic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Patients not responding to MTX after 4 months received Cy orally at 100 mg daily in step two with the same prednisone schedule. In patients showing a partial response, but not a CR, the maximum period of therapy was 1 year.

  • MethotrexateDrug

    Initial treatment consisted of MTX given orally at 10 mg/m2 in divided doses once weekly.

  • PrednisoneDrug

    Prednisone was given orally at 1 mg/kg per day for 30 days and then tapered off in the subsequent 24 days.

Study groups in NCT00003910
Study groupRoleWhat they receive
Methotrexate (Cy if no response to MTX)ExperimentalMTX given orally at 10 mg/m2 in divided doses once weekly. Prednisone was given orally at 1 mg/kg per day for 30 days and then tapered off in the subsequent 24 days. Patients not responding to MTX after 4 months received Cy orally at 100 mg daily in step two with the same prednisone schedule.
Receives: Drug: Cyclophosphamide; Drug: Methotrexate; Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of Patients With Complete or Partial Response to Treatment With MTX

    We will report the overall response rate below. Complete remission requires that all of the following be present for at least four weeks: The patient must have a normal CBC including neutrophil count > 1500/mm3, lymphocyte count< 4000/mm3, hemoglobin > 11 g/dl, and platelet count > 100,000/mm3. In addition, the patient must have a normal LGL count. A complete response will be attained if CD8+ cells were less than 760/mm³. A partial response will be defined as achievement of any one of the following in the absence of CR. The response must last for at least four weeks:In patients being treated for severe neutropenia (less than 500 neutrophils/mm3) an improvement to over 500 neutrophils/mm3 will be considered a partial response, as long as that improvement represents at least a 50% improvement.

    Measured: Assessed during the first 4 months, then at least every three months for two years. Then every six months until five years after study entry, and every 12 months thereafter until full study stop date.

Secondary outcomes (1)

  1. Proportion of Patients With Complete or Partial Response to Treatment of CY Among Patients Failing to Respond to MTX

    We will report the overall response rate below. Complete remission requires that all of the following be present for at least four weeks: The patient must have a normal CBC including neutrophil count > 1500/mm3, lymphocyte count< 4000/mm3, hemoglobin > 11 g/dl, and platelet count > 100,000/mm3. In addition, the patient must have a normal LGL count. A complete response will be attained if CD8+ cells were less than 760/mm³. A partial response will be defined as achievement of any one of the following in the absence of CR. The response must last for at least four weeks:In patients being treated for severe neutropenia (less than 500 neutrophils/mm3) an improvement to over 500 neutrophils/mm3 will be considered a partial response, as long as that improvement represents at least a 50% improvement.

    Measured: Assessed during the first 4 months of treatment and followed until reaching full study stop date

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study start15 Sep 1999
  3. Primary completion1 Dec 2010
  4. Study completionMar 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
59 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00003910
Sponsor's protocol ID
CDR0000067089
Other IDs
U10CA021115, E5998
Status last verified
Jun 2023
First submitted
1 Nov 1999
Last updated
5 Jul 2023
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cyclophosphamide, Methotrexate and Prednisone in people with Leukemia, run by Eastern Cooperative Oncology Group at 68 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 5 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 68 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 May 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Patients With Complete or Partial Response to Treatment With MTX (time frame: Assessed during the first 4 months, then at least every three months for two years. Then every six months until five years after study entry, and every 12 months thereafter until full study stop date.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00003910.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2023.

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